As the number of persons infected with Human Immunodeficiency Virus (HIV) reaches 2 million in the United States, there is growing concern among occupational groups such as health care workers, first responders, sanitation workers, police and firemen that they may become infected with HIV through accidental needlesticks or splashes occurring at work. Nucleoside analogues such as Zidovudine (also referred to as AZT) are offered as prophylaxis to occupational groups following exposure to HIV contaminated materials. Use of dideoxynucleosides, such as ZDV, in healthy populations for prophylaxis has not been examined for potential reproductive or long term mutagenic effects. Such investigation is warranted given that genetic damage in humans and genetic plus reproductive effects have been reported in animals exposed to ZDV, and the data obtained would be of help to individuals and their physicians in making more informed risk/ benefit decisions about the use of this type of prophylaxis following accidental occupational exposures. A cohort study comparing individuals occupationally exposed to HIV who elect to take ZDV or other dideoxynucleoside prophylaxis therapy to a similar occupationally exposed group individuals who do not elect this prophylaxis therapy is being conducted. Cytogenetic effects in blood lymphocytes, and both fertility and cytogenetic parameters in sperm, are being evaluated (repeated measures design) for individuals preparing to start dideoxynucleoside therapy, and during- and post-dideoxynucleoside therapy. Subjects are being recruited from occupational exposures to HIV occurring in the greater Triangle area during a two year period and referred to the Clinical Research Study sites for specimen collection. Additionally, semen and blood specimens are also being collected from HIV infected individuals prior to and during their dideoxynucleoside therapy for use in evaluating cytogenetic and fertility effects of these drugs. During the past year, IRB approvals were renewed from all of the participating hospitals and NIEHS, and 22 patients (20 HIV-positive and 2 occupationally exposed) were enrolled in the study. Fifty-seven (57) blood samples from these 22 individuals were processed for lymphocyte cytogenetic analysis. CASA and standard semen analyses have been performed on 75 samples from the 21 male patients with slides for 57 of these samples thus far submitted to morphology analysis. Epidemiological questionnaires have been completed on each of the patients. A computerized tracking/quality assurance system was designed and implemented and a preliminary analysis of the data is in progress.